The gene
copy number (also "copy number variants" or CNVs) is the number of
copies of a particular gene in the genotype of an individual. Recent
evidence shows that the gene copy number can be elevated in cancer
cells.

The human genome is
comprised of 6 billion chemical bases (or nucleotides) of DNA packaged
into two sets
of 23 chromosomes, one set inherited from each parent. The DNA encodes
roughly 27,000 genes. It was generally thought
that genes were almost always present in two copies in a genome.
However, recent discoveries have
revealed that large segments of DNA, ranging in size from thousands to
millions of DNA bases, can vary in
copy-number. Such copy number variations (or CNVs) can encompass genes
leading to
dosage imbalances. For example, genes that were thought to always occur
in two copies per genome have now been found
to sometimes be present in one, three, or more than three copies. In a
few rare instances
the genes are missing altogether (see figure).

Why
are CNVs important?

Differences in the
DNA sequence of our genomes contribute to our uniqueness. These changes
influence most
traits including susceptibility to disease. It was thought that single
nucleotide changes (called SNPs) in DNA were the most
prevalent and important form of genetic variation. The current studies
reveal that CNVs comprise at
least three times the total nucleotide content of SNPs. Since CNVs
often encompass genes, they may have
important roles both in human disease and drug response. Understanding
the mechanisms
of CNV formation may also help us better understand human genome
evolution.

How
does the new CNV map help?

The new global CNV
map will transform medical research in four areas. The first and most
important area is in hunting for genes underlying common diseases. To
date, attempts to identify these genes have not really considered the
role CNVs may play in human health. Second, the CNV map is being used
to study familial genetic conditions. Third, there are thousands
of severe
developmental defects caused by chromosomal rearrangements. The CNV map
is being used to exclude variation found in unaffected individuals,
helping researchers to target the region that might be involved. The
data generated will also contribute to a more accurate and complete
human genome reference sequence used by all biomedical scientists.

Genetic
diseases are
caused by a variety of different possible alterations (mutations) in
DNA sequences. We are investigating gains and losses of large chunks of
DNA sequence consisting of between ten thousand and five million
letters (known as Copy Number Variation). This type of mutation has
often been overlooked in previous surveys of mutations that cause
genetic diseases. We do not know what proportion of genetic disease is
caused by copy number variation (CNV), but we suspect that it is
appreciable. We already know that many genetic diseases that occur in
families result from these kinds of mutation, we also know that there
are Copy Number Variants that protect against HIV infection and
malaria. The contribution of CNV to the common, complex diseases (e.g.
diabetes, heart disease) is presently unknown.

How much copy number variation (CNV) exists
between human genomes?

How best can CNVs be incorporated into whole
genome association studies?

What is the contribution of copy number
variation to genetic disease?

What is the relative contribution of different
mutational mechanisms to CNV?

DatabasE of Chromosomal Imbalance and Phenotype
in Humans using Ensembl
Resources

The
DECIPHER database
of submicroscopic chromosomal
imbalance collects clinical information about chromosomal
microdeletions/duplications/insertions, translocations and inversions
and displays this information on the human genome map with the aims of: